Lipid-Based Nanocarriers via Nose-to-Brain Pathway for Central Nervous System Disorders

Neurochemical Research - Neurodegenerative disorders are distinguished by the gradual deterioration of the nervous system’s structure and function due to oxidative stress, mitochondrial...     

Alpha-glucosidase inhibitors from Nervilia concolor,Tecoma stans,and Bouea macrophylla

Tecoma stans (L.) Juss. Ex Kunth is widely used in folk medicine. In ethnomedicine, it is applied as a cardioprotective, hepatoprotective, antiarthritic, antinociceptive, anti-inflammatory, and antimicrobial. The aqueous extract is considered antidiabetic, and is used as a traditional remedy in Mexico. More than 120 chemical constituents have been identified in its leaves, barks, and roots. However, less is known about the phytochemical properties of T. stans flower extracts. The herbal plant Nervilia concolor (Blume) Schltr. is native to Vietnam, and is used in traditional Chinese medicine to treat diseases such as bronchitis, stomatitis, acute pneumonia, and laryngitis. Only two previous reports have addressed the chemical content of this plant. Bouea macrophylla Griff., commonly known as marian plum or plum mango, is a tropical plant that is used to treat a range of illnesses. Phytochemical analysis of B. macrophylla suggests the presence of volatile components and flavonoids. However, existing data have been obtained from screening without isolation. As part of our ongoing search for alpha-glucosidase inhibitors from Vietnamese medicinal plants, we conducted bioactive-guided isolation of the whole plant N. concolor, the flowers of T. stans, and the leaves of B. macrophylla. We isolated and structurally elucidated five known compounds from T. stans: ursolic acid (TS1), 3-oxours-12-en-28-oic acid (TS2), chrysoeriol (TS3), ferulic acid (TS4), and tecomine (TS5). Three known compounds were isolated from Nervilia concolor: astragalin (NC1), isoquercitrin (NC2), and caffeic acid (NC3). From B. macrophylla, betullinic acid (BM1), methyl gallate (BM2), and 3-O-galloyl gallic acid methyl ester (BM3) were isolated. All compounds showed promising alpha-glucosidase inhibition, with IC₅₀ values ranging from 1.4 to 143.3 µM. The kinetics of enzyme inhibition showed BM3 to be a competitive-type inhibitor. An in silico molecular docking model confirmed that compounds NC1, NC2, and BM3 were potential inhibitors of the α-glucosidase enzyme. Molecular dynamics simulations were carried out with compound BM3 demonstrating the best docking model during simulation up to 100 ns to explore the stability of the complex ligand–protein.     

Identification of Highly Potent α-Glucosidase Inhibitors from Artocarpus integer and Molecular Docking Studies

A new natural Diels-Alder adduct ( 3 ) was isolated from the leaves and stem bark of Artocarpus integer, along with seventeen known compounds ( 1 , 2 , and 4 – 18 ). Structural elucidation was conducted using NMR and HR-ESI-MS data, and comparisons were made with previous studies. Deoxyartonin I ( 3 ) exhibited the most potent α-glucosidase inhibition (IC₅₀ 7.80±0.1 μM), outperforming the acarbose positive control. This was mixed-mode inhibition, as indicated by the intersect in the second quadrant of each respective plot. An in silico molecular docking model and the pharmacokinetic features of 3 suggest that it is a potential inhibitor of enzyme α-glucosidase, and is therefore a lead candidate as a drug against diabetes mellitus.